The treatment of malignant brain tumors requires a multimodal approach because the disease is still fatal for most patients. We are investigating adjuvant treatment modalities based on the genetic characteristics of the tumors. Due to the high expression of aberrant protein kinase C (PKC) in malignant gliomas and the fact that PKC inhibitors are involved in the induction of apoptosis, we study the efficacy of PKC inhibitors is subcutaneous and intracerebral 9L rat gliomas. The cytokine, interferon-gamma, also induces apoptosis by activating the 2'-5 oligoadenylate synthetase. In vitro studies demonstrated that the combination of PKC inhibitors and interferon-gamma induces apoptosis in 9L glioma cells to a significantly greater degree than either alone. Both the PKC inhibitor safingol and interferon-gamma were well tolerated by rats in the doses used in this study. This study will examine the combination of safingol and interferon-gamma to induce apoptosis in 9L glioma in vivo without significant toxicity. This combination therapy might be a novel adjuvant treatment modality for malignant brain tumors.